Is WAS p.Leu342= (c.1026G>A) pathogenic?

WAS p.Leu342= (c.1026G>A) is classified Likely benign in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). Very rare (popmax 0.00264%, nfe); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Leu342= (c.1026G>A)?

WAS p.Leu342= (c.1026G>A) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Leu342= (c.1026G>A) in the general population?

WAS p.Leu342= (c.1026G>A) is very rare (popmax 0.00264%, nfe) (gnomAD).

How is X-linked severe congenital neutropenia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

WAS p.Leu342=

c.1026G>A · rs2062428535 · VCV2934849

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00264%, nfe)

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.49	GERP -0.81, phastCons 0.99
Overall
CADD	5.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00264% European (non-Finnish) · 23/871,527 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.00197% 23/1,165,616 alleles · very rare exomes 23/1,053,848 · genomes 0/111,768 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: WAS
Protein: p.Leu342=
Coding: c.1026G>A
MANE Select: NM_000377
dbSNP: rs2062428535
Type: single nucleotide variant
Location: chrX:48688754 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 342: the 'disordered' region

Full WAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked severe congenital neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wiskott-Aldrich syndrome thrombocytopenia 1

For X-linked severe congenital neutropenia (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

WAS p.Leu342fs Pathogenic ★ same residue
WAS c.1339-2A>G Pathogenic/Likely pathogenic ★★ same condition
WAS c.1453+2T>C Pathogenic ★★ same condition
WAS c.273+1G>A Pathogenic ★★ same condition
WAS c.360+1G>A Pathogenic ★★ same condition
WAS c.559+5G>A Pathogenic ★★ same condition
WAS c.777+1G>A Pathogenic ★★ same condition
WAS c.778-6G>A Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/was-p-leu342 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown